DESCRIPTION (provided by investigator): Concerns have been raised in the lay and scientific communities that various synthetic chemicals showing hormonal or anti-hormonal properties in vitro and in wildlife populations are causing adverse health effects in humans by interfering with normal endocrine function. A number of the structurally similar halogenated organics belong to this category. Because these chemicals are widespread in the environment and accumulate in human and animal tissues, any associations with adverse health effects could have far reaching public health implications. The Michigan PBB cohort consists of over 4,000 individuals exposed to brominated flame retardants as the result of an industrial accident and has been successfully followed for nearly thirty years. This cohort presents a unique opportunity to determine whether exposure to halogenated organics is associated with endocrine disruption and to evaluate the impact across generations. In the grand tradition of epidemiology we seek to learn as much as we can from an unfortunate "natural" experiment. This applications follows two previous studies of endocrine sensitive endpoints among cohort members conducted by the same team of investigators. In the proposed study we focus on the offspring of cohort members where we have found the greatest evidence of endocrine disruption. Specific Aim 1 continues our assessment of the consequences of in utero exposure among males. We previously found that sons of highly exposed women experienced an increased risk of genitourinary conditions and slower growth and pubertal development. Specific Aim 2 addresses endocrine-sensitive endpoints among female offspring following evidence that highly exposed girls have an earlier age at menarche and an increased risk of miscarriages. In Specific Aim 3 we seek to characterize the cross-generational transfer of brominated flame retardants and Specific Aim 4 is an exploration of interdisciplinary approaches to understand biological mechanisms of multi-generational endocrine disruption and gene/environmental interactions. PUBLIC HEALTH RELEVANCE: Brominated flame retardants are ubiquitous in the modern environment however the consequences of chronic exposure to humans are unclear. Studying the health of the Michigan PBB cohort (who were exposed to brominated flame retardants through an unfortunate industrial accident) and their children provides important information regarding exposure to chemicals that may disrupt the endocrine system across generations. Findings from the study of this unique and dedicated cohort may lead to important information about the health effects of brominated flame retardants and other related chemicals that are still in production today.